Ginsenoside Rb1-enhanced decellularized extracellular matrix hydrogels ameliorates mitochondrial dysfunction and...

Area of Science:

• Biomaterials Science
• Cellular Biology
• Regenerative Medicine

Background:

• Sepsis-induced acute lung injury (ALI) presents a critical health challenge with high mortality and few effective treatments.
• Cellular senescence and mitochondrial dysfunction in alveolar type II (AT2) cells are key factors in ALI development.
• Ginsenoside Rb1 shows promise in addressing cellular aging and mitochondrial health.

Purpose of the Study:

• To assess the therapeutic potential of Rb1-loaded decellularized extracellular matrix hydrogel (dECM-gel) for sepsis-induced ALI.
• To investigate the effects of Rb1-loaded dECM-gel on cellular senescence and mitochondrial function in AT2 cells.
• To evaluate the in vivo efficacy of Rb1-loaded dECM-gel in a murine model of ALI.

Main Methods:

• Formulation and rheological characterization of Rb1-loaded dECM-gel.
• In vitro assessment of AT2 cell senescence, mitochondrial function (JC-1, ATP assays), and oxidative stress.
• In vivo evaluation in a murine sepsis-induced ALI model, analyzing lung histopathology, oxidative stress, and apoptosis.
• Investigation of underlying molecular pathways, including mitochondrial unfolded protein response (mtUPR) and AMPK/SIRT1 signaling.

Main Results:

• Rb1-loaded dECM-gel significantly reduced AT2 cell senescence and improved mitochondrial function.
• The treatment enhanced mitochondrial membrane potential and ATP levels, alleviating structural damage.
• In vivo studies showed improved lung histopathology, reduced oxidative stress, and decreased apoptosis.
• Therapeutic effects were linked to the activation of mtUPR and the AMPK/SIRT1 pathway.

Conclusions:

• Rb1-loaded dECM-gel effectively mitigates sepsis-induced ALI through mtUPR enhancement and AMPK/SIRT1 pathway activation.
• This ginsenoside-based biomaterial represents a promising therapeutic strategy for lung injury.
• The findings highlight the potential of advanced biomaterials in ALI clinical management.